Anastrozole

Is anastrozole safe?

For women past the menopause with hormone-sensitive breast cancer, anastrozole is a safe and well-studied choice, and on most serious harms it does better than tamoxifen. The price is paid in bones and joints. In the ATAC trial of 9,366 women, it prevented more recurrences than tamoxifen, with fewer clots and far fewer womb cancers, but more fractures while women were taking it.

Joint pain is what most women actually notice, and it is the main reason people stop early. There are few drug interactions to worry about, and an overdose of the tablets is not known to be dangerous.

We score anastrozole 81, the same as letrozole, the other aromatase inhibitor in wide use. That is well above tamoxifen's 69, mainly because it has no boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary and none of tamoxifen's womb cancer, clot or antidepressant problems.

Anastrozole vs tamoxifen: what the ATAC trial found

ATAC compared five years of anastrozole 1 mg with tamoxifen 20 mg after surgery. After 10 years of follow-up, women with hormone-receptor-positive cancer on anastrozole had 21% fewer recurrences, and the gap kept widening for some years after treatment ended: 2.7 percentage points at 5 years and 4.3 at 10. Deaths from all causes were similar in the two groups.

The side effects pulled in opposite directions:

A pooled analysis of 31,920 women by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) found the same pattern across all aromatase inhibitors: a 5-year fracture risk of 8.2% against 5.5% on tamoxifen, a 10-year womb cancer risk of 0.4% against 1.2%, and about 15% fewer breast cancer deaths over 10 years.

Bones, joints and the heart

Anastrozole works by blocking aromatase, the enzyme that makes oestrogen after the menopause. Less oestrogen means bone thins faster. In ATAC, the extra fractures stopped once treatment ended. The labels advise a bone density scan at the start and at intervals for women at risk, and the US label notes that a bisphosphonate preserved bone density in most women at risk of fracture.

Joint pain and stiffness are very common. In ATAC, 15% of women on anastrozole reported joint pain against 11% on tamoxifen. In a US study of 503 women starting an aromatase inhibitor, 32% stopped within two years because of side effects, 24% because of joint and muscle symptoms. Carpal tunnel syndrome, trigger finger, tendonitis and tendon rupture are also listed.

The heart is the open question. In ATAC as a whole, ischaemic heart events were 4% against 3%, but among women who already had heart disease they were 17% against 10%, which is why the US label asks doctors to weigh this. A 2011 meta-analysis found longer use of aromatase inhibitors linked to more heart disease than tamoxifen, about one extra case for every 132 women treated. Tamoxifen itself lowers total and LDL cholesterol by about 10–20% in women past the menopause (UK tamoxifen label), so part of that gap may reflect tamoxifen protecting rather than anastrozole harming. In IBIS-II, which used a placebo, no excess of heart disease was seen.

Anastrozole to prevent breast cancer

IBIS-II gave anastrozole or placebo for five years to 3,864 healthy women past the menopause at raised risk. After a median of 131 months, breast cancers were 85 against 165, a 49% cut, with no difference in deaths. Joint pain (51% against 46%) and hot flushes (57% against 49%) were only modestly more common than on placebo.

NICE now advises offering anastrozole for five years to women past the menopause at high risk unless they have severe osteoporosis, and considering it at moderate risk. The MHRA added prevention to its UK licence on 6 November 2023. In the US, the label covers treatment only.

Overdose, interactions and misuse

Single doses of 60 mg, 60 times the daily dose, were tolerated in volunteers, and no overdose deaths are described. There is no antidote, so care is supportive. Get advice after any large overdose: Poison Help on 1-800-222-1222 in the US, NHS 111 in the UK.

The interactions that matter are simple. Tamoxifen lowered anastrozole levels by 27% and the combination added nothing in ATAC, and oestrogen-containing medicines, including HRT, can blunt it. Anastrozole did not change the effect of warfarin in a volunteer study. It is not addictive, and the World Anti-Doping Agency bans it in sport at all times.

Who should be careful

Talk to your oncology team or pharmacist before starting anastrozole, or adding a medicine to it, if you:

• may not be past the menopause; the UK label says to confirm it with blood tests when in doubt
• have osteoporosis, past fractures or other risks for weak bones
• have heart disease or high cholesterol
• take HRT, vaginal oestrogen or any other oestrogen product
• could become pregnant or are breastfeeding; the UK label rules out use in pregnancy and breastfeeding, and the US label advises contraception during treatment and for 3 weeks after the last dose
• have moderate or severe liver disease

A lower score than some everyday medicines is no reason to stop anastrozole. Any change belongs with your oncology team.

How we scored it

Dependence (98), track record (95) and overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (92) are strong, and interactions (85) are few. Serious side effects (60) reflect fractures, frequent joint pain and the heart signal in women with heart disease, offset by fewer clots and womb cancers than tamoxifen. Regulatory warnings (80) reflect label warnings without a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary.